Congenital idiopathic hypogonadotropic hypogonadism (IHH) is a disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary ... Congenital idiopathic hypogonadotropic hypogonadism (IHH) is a disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary axis. Idiopathic hypogonadotropic hypogonadism can be caused by an isolated defect in gonadotropin-releasing hormone (GNRH; 152760) release, action, or both. Other associated nonreproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss, occur with variable frequency. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism has been called 'Kallmann syndrome (KS),' whereas in the presence of a normal sense of smell, it has been termed 'normosmic idiopathic hypogonadotropic hypogonadism (nIHH)' (summary by Raivio et al., 2007). Because families have been found to segregate both KS and nIHH, the disorder is here referred to as 'hypogonadotropic hypogonadism with or without anosmia (HH).' For a discussion of genetic heterogeneity of hypogonadotropic hypogonadism with or without anosmia, see 147950.
Kim et al. (2010) screened 123 normosmic and hyposmic/anosmic HH patients for mutations in 3 candidate genes on chromosome 10q26, but identified no causative mutations. Sequencing a fourth candidate gene, WDR11 (606417), in 201 normosmic or hyposmic/anosmic HH ... Kim et al. (2010) screened 123 normosmic and hyposmic/anosmic HH patients for mutations in 3 candidate genes on chromosome 10q26, but identified no causative mutations. Sequencing a fourth candidate gene, WDR11 (606417), in 201 normosmic or hyposmic/anosmic HH patients, they identified 5 different heterozygous missense mutations in 6 unrelated probands, including 5 normosmic patients (see, e.g., 606417.0001 and 606417.0002) and 1 anosmic patient (606417.0003). DNA from the parents was unavailable, but the mutations were not found in more than 400 controls.